Immunogenicity and antitumor activity of a liposomal MUC1 peptide-based vaccine.
A human MUC1-transfected mouse mammary adenocarcinoma cell line (GZHI) was used to develop both subcutaneous and intravenous tumor models. A vaccine formulation comprised of a 24 mer (human MUC1) synthetic peptide encapsulated with monophosphoryl lipid A adjuvant (MPLA) in multilamellar liposomes was tested for immunogenicity and anti-tumor activity. A low dose of the human MUC1 peptide (5 microg) administered in liposomes provided excellent protection of mice in both tumor challenge models. The protective antitumor activity mediated by the liposome formulation correlated with anti-MUC1-specific T-cell proliferation, gamma-interferon (IFN-gamma) production and IgG2a anti-MUC1 antibodies, suggesting a type 1 (T1) T-cell response. In contrast, lack of protection in mice immunized with negative control vaccines correlated with IgG1 anti-MUCI antibody formation, low or no anti-MUC1 IgG2a and low antigen-specific T-cell proliferation, consistent with a type 2 (T2) T-cell response to the tumor.
Samuel
J
J
Faculty of Pharmacy, University of Alberta, Edmonton, Canada.
Budzynski
W A
WA
Reddish
M A
MA
Ding
L
L
Zimmermann
G L
GL
Krantz
M J
MJ
Koganty
R R
RR
Longenecker
B M
BM
D000595:Amino Acid Sequence; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D018396:Mucin-1 / Q000008:administration & dosage / Q000276:immunology*; D009374:Neoplasms, Experimental / Q000517:prevention & control*
D019496:Cancer Vaccines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008081:Liposomes; D018396:Mucin-1